Endovascular aneurysm repair is an alternative to surgical repair of abdominal aortic aneurysm which enables to reduce patient operating risks and time of recovery. However, this treatment is presently limited by the persistence of blood leaks (called endoleaks). Some of these endoleaks (type II endoleaks) can be treated by injecting an embolizing agent to block blood flow.
Several embolizing agents (mainly N-butyl-2-cyanoacrylate (NBCA) [1-4], Ethylenevinyl alcohol copolymer (EVOH, Onyx® [5, 6], polyurethane fragments and fibrin glue [7], combined or not with coils [4, 8]) have been tested recently for the treatment of endoleaks or for their prophylactic prevention by injection into the aneurismal sac. Although these studies showed that sac embolization has potential to minimize endoleak occurrence, they also show that materials existing presently are limited. Recurrence of endoleaks are frequent. It is believed to be due to recanalisation process through or around the injected materials. The same limitation occurs when prophylactic injection of embolizing agent around the implant is performed in order to prevent endoleak formation [3, 9, 10]. It is believed that combining embolizing and sclerosing properties would improve clinical results by inducing endothelial denudation and thus preventing recanalisation processes and promoting fibrosis and healing. The only commercialized embolizing agent that may present sclerosing properties to date is cyanoacrylate. However this agent is not biodegradable and such embolizing agent do not exist presently or they do not present adequate mechanical and biodegradation properties.
In the case of arteriovenous malformation, sclerosing agents such as ethanol and sodium tetradecyl sulphate foams are already used to permanently occlude the vessels. However, these agents are far from ideal since their poor mechanical properties make injection difficult to control and do not enable to efficiently occlude blood flow.
Endovascular aneurysms repair (EVAR) clinical outcome is severely limited by the persistence of blood flow perfusing the aneurysm, called endoleaks, observed in 10% to 36% of cases [14-17]. The most frequent type of endoleak is type II endoleak, which corresponds to retrograde flow from collateral arteries [18, 19]. Persistent type II endoleaks with sac size progression require interventions as they can lead to aneurysm rupture [14, 15, 17, 18, 20-26]. Several attempts have been recently made to treat or prevent type II endoleaks using coils or polymeric embolising agents (mainly N-butyl-2-cyanoacrylate (NBCA) [1-4], Ethylenevinyl alcohol copolymer (EVOH, Onyx® [5, 6], polyurethane fragments [27] and fibrin glue [7], combined or not with coils [4, 8]. These studies showed that sac embolization has potential to minimize endoleak occurrence. However, embolization failure (recurrence, recanalisation) was reported with all tested agents. Prophylactic embolization of the inferior mesenteric and/or lumbar arteries or of the entire aneurismal sac during EVAR has also been proposed in patients to prevent endoleak formation, once again with limited success [3, 9, 10]. Uflacker et al. reported a high proportion of residual leaks in an animal model despite deacetylated glucosamine injection into the aneurysm [28]. In a human study, injection of fibrin glue decreased the rate but did not completely prevent type II endoleaks (2.4%) [7]. Injectable agents developed to date are not only unable to treat or prevent all endoleaks. They are also far from ideal for such clinical use. Cyanoacrylate and Onyx are difficult to control during injection, are non-biodegradable and non porous, thus preventing tissue healing in the cast. Their long-term biocompatibility is questionable. Moreover they are also very radiopaque and could create a diagnostic challenge in surveillance imaging studies. The two components of fibrin glue must be injected separately and cannot easily fill up the cavity, since they immediately form a blood clot.
Accordingly, there is a need in the industry to provide a gel for repairing aneurysms and other vascular defects. An object of the present invention is therefore to provide such a gel.